The present invention relates to substantially non-leachable sol-gel particles and, more particularly, to sol-gel micro- and nanoparticles encapsulating one or more agents (e.g., colorants), characterized by unprecedented stability to leaching or migration of the agents from therein. The present invention further relates to a method of producing the particles of the invention and to products containing the particles of the invention, such as, for example, cosmetic, and oral care colored products.
Coloring agents, which are also referred to herein as colorants, such as dyes, pigments, colors and lakes are well known in the art and are widely used in a variety of fields. However, as many of the presently known colorants are toxic, chemically reactive and/or water soluble, their use is severely limited.
“FD&C” and “D&C” colors are colorants that are allowed for use in food, drugs and cosmetics by governmental regulatory authorities, such as the FDA. These colors are typically water-soluble and as such, their applications are often limited by their tendency to leach into parts of the formulation where their presence is undesired (for example, in striped toothpaste) or to form complexes with other ingredients, such as, for example, proteins, which are present in the formulations.
“FD&C” colors can be formulated as lakes, where they are adsorbed on inorganic substrates such as alumina, titania or zirconia. U.S. Pat. No. 4,444,746 teaches, for example, the use of such lakes in dentifrices. The lake is dispersed throughout a dentifrice medium and is aimed at preventing dissolution of the water-soluble dye. Nevertheless, while lakes may be useful in preventing the dissolution of water-soluble colors, they do not prevent the colors migration to the surrounding medium.
Colors and dyes which do not belong to the “FD&C” colors can optionally be used in some cosmetic applications. However, due to the relative toxicity of such coloring agents, their use is limited by the proviso that they would not contact the skin.
Other water-based colors, dyes or lakes, which are excluded for use in food, drugs and cosmetics, are used in various industrial applications. The use of such industrial colors is often limited by their high chemical reactivity, which results in high susceptibility thereof to chemical/photochemical attack.
One of the prevalent ways to overcome the limitations associated with using coloring agents in various applications is external encapsulation of the colorants. External encapsulation of colors, dyes and lakes may prevent undesired leaching and/or contact and may further protect the colorants from other environmental components, thereby increasing their applicable value.
However, apart from providing protection and preventing leaching and/or contact of the colorants, efficient and applicable colorants encapsulation further depends on other parameters such as particles size, particles shape, transparency, toxicity of the encapsulating matrix and more, particularly in cases where the encapsulated colorants are used in oral care, pharmaceutical and/or cosmetic products.
More specifically, a preferred size of colorant-containing particles is in the several microns range. Using colored particles that have lager size, e.g., over 10 microns, is undesired since mixing such particles with formulations for oral care (e.g., toothpaste) and cosmetics would result in dots-like colored medium, rather than continuously colored product. Moreover, the tinting power of large pigments is severely affected by large particles size. In addition, large particles usually impair a gritty feeling, which is highly undesirable in, for example, cosmetic products.
Particles encapsulating colorants should further preferably have a spherical shape, which provides for a better feeling of the final product and for a continuous coloring effect.
The encapsulating medium should also be transparent, so as to maintain the coloring effect of the encapsulated colorant.
Encapsulation of different ingredients can be obtained using both organic and inorganic matrices. Typical organic matrices include organic and bioorganic polymers. Such polymers are inherently more susceptible to chemical and photochemical damage as compared with inorganic polymers and are highly sensitive to shear forces, osmotic pressure, heat, etc. Therefore, organic matrices typically tend to release the ingredients contained therein into the surrounding medium, hence failing to supply sufficient stability and localization of the colored product. Furthermore, many of the presently known organic matrices used for encapsulation of water-soluble ingredient are often characterized by relative toxicity, which prevents their use in, for example, food, drug, oral care and cosmetic formulations. Thus, encapsulation of colorants in inorganic matrices, which are typically more stable and often less toxic, is preferable.
External encapsulation of coloring agents has been practiced to some extent, using both organic and inorganic encapsulation matrices and typically involves the production of water-insoluble pigments containing water-soluble colorants.
U.S. Pat. No. 4,769,080, for examples, teaches the use of a layered anion exchange material, preferably an aluminate, which is contacted with a liquid medium containing the dissolved dye, to thereby adhere the dye within the layered material.
GB Patent No. 1,319,991 teaches preparation of colored resins containing non-toxic water-soluble dyes as a water impervious cross-linked synthetic resin for use in toothpastes. Water-soluble monomers such as urea formaldehyde, melamine formaldehyde, melamine-urea formaldehyde and phenol formaldehyde are used according to the teachings of this reference to form the water-insoluble resins. However, it should be noted that, as is well known in the art, formaldehyde is a toxic agent and hence its use in, for example, oral care and cosmetic products is highly undesirable as traces thereof can be released over time.
U.S. Pat. No. 5,756,073 discloses a striped dentifrice (e.g., a paste or gel) in which the colorant is loaded within a substantially non-fracturable matrix of a partially cross-linked melamine-urea-formaldehyde polymer. The polymer is in the form of particles having a size range of from about 2 to 70 microns. The dentifrice, according to the teachings of this reference, may also contain a scavenger compound, which is aimed at inactivating or binding up any un-reacted cross-linking agent (i.e., formaldehyde). The inclusion of such a scavenger in the formulation demonstrates the severe limitations associated with the incorporation of formaldehyde-containing polymers in, for example, oral care products.
U.S. Pat. No. 4,069,311 discloses the formation of small colored globules or particles, obtained by dispersing a speckling material and a binder such as a thermoplastic resin, gum, gel, paraffin, wax, polymer and high fatty acid and salts thereof, in water. The speckling material used in this patent is evidently water-insoluble and hence this method cannot be used with water-soluble coloring agents such as the FD&C colors.
U.S. Pat. No. 4,533,484 also teaches a method of preparing water-insoluble pigment particles, which is effected by contacting water-soluble dyes with a polymer that comprises an alkyl-2-oxazolidinone moiety.
WO 97/18267 and U.S. Pat. No. 6,037,000 teach a process of encapsulating colored lakes within a substrate such as a high-density polyethylene material, by means of melt and spray-congealing, in which particles that are substantially impervious to water or other solutes of choice are formed. A secondary coating comprised of another substance, such as petrolatum, may optionally be added to the matrix so as to virtually eliminate dye migration. According to the teachings of these references, the size of the obtained pigment particles ranges between 5 and 35 microns. As is discussed hereinabove, such relatively large particles are undesirable in most of the colored formulations. As it is well known in the art that particles formed by spray-congealing processes have a size of at least few microns, it is impossible to produce by the process described in these references smaller particles.
Similarly, U.S. Pat. Nos. 5,876,701 and 6,315,986 disclose a lake-containing striped dentifrice in which the lake is stabilized by entraining in wax or in high-density polyethylene matrices in a melt process. As this process involves the same general technique used in WO 97/18267 and U.S. Pat. No. 6,037,000, the obtained particles are evidently of large size and hence the use thereof is limited.
All the formulations described hereinabove employ organic or bioorganic matrices for encapsulating the colorants. As is further discussed hereinabove, the use of such matrices is often limited due to their relatively poor stability and toxicity. Furthermore, some of the processes described hereinabove are further limited by the relatively large size of the particles produced thereby.
As is further discussed hereinabove, inorganic polymers often present a better choice as encapsulation matrices for colorants, particularly in cases where the colored products are directed to food, drug, oral care or cosmetic applications. Silica, which is also known by its chemical name silicon dioxide, is one of the presently preferred inorganic substances that can be used as an encapsulation matrix for such applications, as it is a safe and stable chemical, which is allowed for use in food products (see, for example, Federal Register, Volume 67, Number 94 and 40CFRo Part 180, 2002).
U.S. Pat. No. 6,074,629 discloses a dentifrice containing dye-absorbing amorphous silica granules. The granules are characterized by linseed-oil absorption of at least about 150 cc/100 grams and by an average particle size of about 400 micron to about 600 micron and can be either spherical or non-spherical. The amorphous silica granules serve as an absorbent of an FD&C dye or other coloring agent, so as to form a darker portion of the dentifrice, such that a speckled appearance of the dentifrice is obtained. As is discussed hereinabove, the large particles produced by such a process result in a final product that is characterized by both grittiness and possible abrasiveness. Furthermore, as the process involves absorbance of the colorant by the silica granules from a mixture containing all the components comprising the dentifrice, the silica granules cannot serve as an efficient matrix for preventing leakage and migration of the dye.
U.S. Pat. No. 6,143,280 also teaches a method of adhering dye to silica particles. Porous silica slurry is used as a substrate for deposition of colorant-containing aluminum hydroxide within the pores. The product is then milled to obtain non-spherical particles having a size of 5 to 15 micron. Again, such a process results in large and non-spherical particles, which affect both the feeling and the coloring effect of the final product.
EP 0 581 651 teaches a method of producing spherical fine particles having a coloring pigment enclosed therein. The method involves coating of the pigments with a metal oxide either by an interface reaction process or by preparing a gel from an aqueous solution of metal oxide sol. The pigments used in this method are water-insoluble organic or inorganic pigments. The metal oxide coating provides for spherical shape of the particles, which contributes to even dispersion of the particles in make up formulations, and affords the desired vivid color. The size of the final particles is 0.1 to 50 micron in diameter, as required for obtaining the desired feeling and coloring effects. Nevertheless, EP 0 581 651 fails to teach a method of encapsulating water-soluble colorants, and hence the method described therein cannot be utilized with colorants such as FD&C colors, which, as stated above, are water-soluble colorants.
Japanese Patent Application No. 7-238983 discloses a cosmetic material that contains a colored metal oxide gel. The gel is produced by adding a metal alkoxide to a water-in-oil type emulsion containing a water-soluble colorant. The metal oxide gel is obtained in the form of spherical particles, having a size of 0.1 to 500 micron. The approach utilized in this reference, namely, formation of colored particles via a sol-gel process, is aimed at producing colored particles which are spherical, having a relatively small size and are capable of preventing leaching and/or migration of the colorant. However, as is discussed in detail hereinbelow, although such a method of encapsulating colorants appears to produce particles that are characterized by all the parameters required for efficient encapsulation, while considering the limitations that typically accompany encapsulation of various ingredients by such a sol-gel process, it is unlikely to expect that such particles would completely prevent leaching and/or migration of the encapsulated colorant. In this respect it should be noted that although this reference teaches the stability of the colored spheres upon heating in air, it fails to teach whether the obtained spheres can prevent leaching of the dye therefrom in various formulations.
Preparation of spherical hydrous silica oxide particles under acidic conditions is also described by Aizawa et al. [M. Aizawa, S. Kitajima, M. Ohsawa and W. Yang, J. Sol-Gel Sci. Tech. 19, 329-332, 2000]. Particles of 10 to 100 microns entrapping Rhodamine 6G, a hydrophilic dye, are prepared in emulsions, using tetraethyl orthosilicate (TEOS), ethyl acetate and acetic acid/water system, and hydrochloric acid as a catalyst. The particles obtained by this process are dense and clear and its final shape, i.e., spherical particles, non-spherical powder or homogeneous solutions, is determined by the TEOS/ethyl acetate/acetic acid ratio used. The process disclosed in this reference is also based on a simple sol-gel process which, as is discussed hereinabove, typically fails to provide non-leachable particles.
Barbe et al. [C. Barbe, R. Beyer, L. Kong, M. Blackford, R. Trautman and J. Bartlett, Controlled Release Society 29th annual meeting proceedings, No. 293] also teach the preparation of silica microspheres and nanospheres entrapping a colorant. According to the teachings of Barbe et al., water-in-oil emulsions of the dye Orange II, tetramethyl orthosilicate (TMOS), methanol, water and surfactants are used to form silica spheres entrapping the dye, using either acidic or basic catalysis. The size of the obtained spheres is between 50 nm to 50 microns. However this reference further teaches, upon investigating the release kinetics of the dye from the spheres, that such a system can serve for controlled release applications since the obtained particles were found to release the entrapped dye. The research conducted by Barbe et al. demonstrates the inefficiency of silica particles obtained by a simple sol-gel process to completely prevent leaching and/or migration of the dye therefrom.
Hence, although the prior art teaches various methods for encapsulating water-soluble colorants, none of these methods provides a product which is non-toxic, evenly colored and is further characterized by small particles size, spherical particles shape and ability to prevent leaching and/or migration of the entrapped colorant.
As these parameters are all required for efficient use of the encapsulated colorant in various applications, such as, for example, oral care, food, drug and cosmetics applications, there is a widely recognized need for, and it would be highly advantageous to have, a method of encapsulating colorants devoid of the above limitations. The development of such a method can be further utilized for producing leachless particles that encapsulate other agents while preventing their leaching.